Histopathological study of meningioma in a tertiary care centre: a two years experience

Background: Meningioma is a neoplasm arising from the arachnoidal cap cells in the meningeal coverings of the spinal cord and brain. These are the most common benign intracranial tumours and account for about 13-26% of all primary brain neoplasms. These are generally benign neoplasms, but about 10% are atypical or malignant. Objective: To study the variants and histopathological spectrum of meningioma. Material & Methods: This study includes 29 cases of meningioma diagnosed over a period of two years. Result: Most common variant was noted to be meningothelial meningioma followed by transitional meningioma. Out of the 29 cases, grade I were 96.55% whereas grade II were 3.44%. Conclusion: From our study, we conclude that meningothelial meningioma is the most common variant. Benign meningiomas are the most common type.


Introduction
The term 'Meningioma' was coined by Harvey Cushing in the year 1922. Meningiomas are the most common primary intracranial neoplasms arising from the leptomeninges. These account for about 13-26% of all primary brain neoplasms [1]. These are predominantly located in the cerebral hemisphere, but occurrence at other sites has also been noted. Most of the meningiomas are benign and are categorized as WHO grade I. Atypical meningiomas account for about 4.7-7.2% of meningiomas; whereas anaplastic meningiomas comprise between 1.0-2.8% of meningiomas [2,3].
The origin of meningioma is thought to be from the arachnoidal cap cells in the meningeal coverings of the brain and spinal cord [4].Meningiomas have dural attachment and are well-demarcated rounded or lobular masses. Parafalcine meningiomas are usually irregular, dumbbell shaped [5].En plaque meningioma is a specific clinicopathological entity, which is locally invasive, but usually is histologically benign. These are usually located in sphenoidal region, calvarium and spinal region and grow in a sheetlike pattern [6]. A small Manuscript received: 2 nd January 2019 Reviewed: 10 th January 2019 Author Corrected: 16 th January 2019 Accepted for Publication: 20 th January 2019 number of meningiomas tend to lack circumscription and involve the adjacent brain parenchyma indicating aggressive nature of tumour. Cut surface of meningioma may vary depending upon the histological features. These are usually light tan to brown in colour. Angiomatous meningioma has a haemorrhagic appearance due to prominence of vascular channels. Microcystic meningiomas usually have a soft and spongy texture due to presence of numerous small cystic spaces [7].
Histological grading of meningioma is known to have prognostic and therapeutic implications. Histologically, meningiomas show considerable heterogeneity. Several histological features are associated with either benign or aggressive behaviour. Various histological features that are included for diagnosis and classifying meningioma include tissue pattern, cellular morphology, mitotic activity, necrosis, presence of psammoma bodies, and infiltration of underlying brain parenchyma. Features taken into consideration for higher grading of meningioma include mitotic rate, high cellularity, small cell change (high nuclear to cytoplasm ratio), macronucleoli, pattern less growth, foci of necrosis and brain invasion [4]. Mitotic count is assessed in the areas of highest mitotic count, calculating number of mitotic figures in ten consecutive non-overlapping high power fields. Sheeting is defined as lack of typical meningioma growth patterns, and is noted when this covers more than half of the field at 10X magnification.

Original Research Article
Macronucleoli are said to be present when they are recognized at 10 X power.
Small cell formation is characterized by high nuclear to cytoplasm ratio. Many other studies correlated several histological features like fibrosis, hyper vascularization, nuclear pleomorphism, apoptosis, vesicular nuclei, presence of lymphocytes, lipidization, etc [4].
The WHO classification of tumours of the central nervous system [2] determines 15 separate histopathological variants of meningiomas that correspond with 3 grades of malignancy: benign meningiomas (grade I), atypical meningiomas (grade II) and malignant meningiomas (grade III) [2,8].
An update of the 2007 WHO classification was introduced in 2016. In which brain invasion was introduced as a criterion for the diagnosis of atypical meningiomas, WHO grade II, which can alone suffice for diagnosing an atypical meningioma [9]. The aim of this study is to classify meningioma and its variants based on histology.

Material and Methods
Study design: A hospital based retrospective study was undertaken which included 29 diagnosed cases of meningioma. This study has been carried out in a tertiary care hospital in Mumbai over a period of two years.

Sample collection & method:
The hematoxylin and eosin stained sections were studied. Special stains were taken into consideration wherever needed. Microscopic features were studied and criteria outlined in the latest WHO Classification of Tumours of CNS 2016 were used for diagnosis and categorization of meningioma.
Inclusion criteria: Patients diagnosed as Meningioma during the study period in the Department of Pathology were included.
Exclusion criteria: Patients with inadequate biopsy specimen and the specimens with diagnosis other than Meningioma.
Statistical analysis: Data was analysed in the form of tables and percentage.
Among the 29 cases, 20 were female and 9 were male. Male: female ratio was 1:2.2. Thus, female predominance was noted. Most common age group affected was 31-60 years, consisting of 18 cases out of 29 (Table 3).

Discussion
Meningiomas have heterogenous histological picture and are divided into three grades according to WHO classification of tumours of the central nervous system. The results in both these studies were similar to our study. Many other studies in literature found grade I to be the most common type of meningioma [12]. Meningothelial, Transitional and fibrous meningioma constitute the most common variants in many studies ( There were 3 cases (10.34%) of angiomatous meningioma in our study. Study done by Desai et al [14] showed similar results by noting 9.09% cases of angiomatous meningioma. This type is characterized by abundance of blood vessels. The blood vessels were variable in size with some vessels showing increased wall thickness and others were thin walled. At places, the meningothelial component was suppressed due to the abundance of blood vessels. Angiomatous meningioma is a rare variant of meningioma. MRI shows some typical features like perilesional edema due to increased vascularity [15].
Other subtypes in our study include one case each of fibrous, secretory and atypical meningioma (3.44%). Histologically, fibrous meningioma consisted of spindle cells arranged in storiform pattern and interlacing bundles.
Collagen rich matrix was also seen. Secretory meningioma demonstrated intracellular lumina with presence of eosinophilic secretions within showing positivity with PAS staining. These cases accounted for 1.35% in the study done by Wang et al [16] and 2.96% in the study by Regelsberger et al [17], which were in concordance with our study. We did not find other variants of grade I meningioma i.e. microcystic, lymphoplasmacyte-rich and meta plastic during our study period. Atypical meningiomas include types having certain histological parameters that are associated with increased risk of recurrence and more aggressive behaviour than benign forms.
These include meningioma with (a) mitotic index more than 4 per 10 high power fields OR (b) 3 of the 5 features which include-patternless growth, hyper cellularity, high nucleus: cytoplasm ratio, macronucleoli and geographic areas of necrosis OR (c) Brain invasion. The case of grade II atypical meningioma in our study demonstrated presence of brain invasion. Brain invasion is defined as irregular tongue-like protrusions of tumour cells infiltrating into the underlying brain parenchyma without an intervening layer of leptomeninges [18]. Other specific subtypes included in grade II are chordoid and clear cell meningioma.
The most aggressive form fall into grade III which include anaplastic, rhabdoid and papillary meningioma. These account for 1.0-2.8% of meningiomas. The criteria for anaplastic meningioma includes: Mitotic index ≥20 mitosis/10 HPF or features of anaplasia (sarcoma, carcinoma or melanoma like histology) [2]. During our study period, we did not find any grade III case.
Most common age group affected in our study was 31-60 years with a female predominance. Immunohistochemistry (IHC) mainly has a role in differential diagnosis, for example, when distinguishing meningioma from hemangiopericytoma or other mesenchymal tumours. Majority of the meningiomas stains positive for epithelial membrane antigen (EMA). Vimentin positivity is also seen in all meningiomas. The intermediate filaments in meningiomas that are composed of vimentin give a consistent positive immunostaining with antibodies to this protein.
Variable positivity is seen for S-100. Secretory meningiomas demonstrate a characteristic positivity for cytokeratin and carcinoembryonic antigen. Some of these tumours also show positive staining for other IHC markers including claudin-1, CD99, bcl-2 and Factor XIIIa have also been noted in some of these tumours [5]. An important role for immunohistochemistry in meningioma diagnostics lies in the assessment of the proliferative index, which in clinical pathology is usually measured with the antibody MIB-1. MIB-1 is

Original Research Article
Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.medresearch.in 4 | P a g e the clone that targets the proliferation marker Ki-67 in paraffin embedded tissue. Raised MIB-1 labelling indices are associated with increased risk of recurrence. Demonstration of progesterone receptors also have a role in meningiomas [19]. Many studies have demonstrated higher PR expression in benign compared to aggressive forms. It was also reported that positive progesterone receptors are associated with less recurrence rate. These have inverse relationship with Ki-67 proliferative index, and thus associated with better prognosis [21]. Asimmunohisto chemistry was not available at our institute; patients were referred for IHC to the oncology institution.

Conclusion
Meningiomas are predominantly benign neoplasms of the central nervous system. Histopathological examination is an imperative tool for confirmatory diagnosis due to the diverse histological variants. Also, the prognosis of the disease depends on histopathological grading of the lesion.
The accuracy of histopathological diagnosis and grading of meningioma requires a continuous revision of histopathology. Continual revision of grading systems is essential to improve the diagnostic accuracy, as was introduction of brain invasion criteria in grade II meningioma.
Our distribution of histomorphologic spectrum of meningioma is similar to most of the other studies worldwide as stated in discussion. However we had only few cases of atypical meningioma as compared to others. Genetic profiling and Immunohistochemistry in prospective study may provide more details and elaborate the facts.

Author contribution
 Dr. Shalaka Khade contributed to study designing, literature search and review, data acquisition and analysis, statistical analysis, manuscript preparation and editing.
 Dr. Ramesh Waghmare contributed to study designing, literature review, data analysis, manuscript preparation and editing.
 Dr. Asha Shenoy contributed to study designing, literature review, data analysis, manuscript preparation and editing. Consensus of all authors was reached in finalization of draft for publication.